The present invention relates generally to the field of microwave-assisted chemistry techniques, and in particular relates to techniques of monitoring microwave-assisted chemical reactions.
Microwave-assisted chemistry techniques are generally well established in the academic and commercial arenas. Microwaves have some significant advantages in heating (or otherwise supplying energy to) certain substances. In particular, when microwaves interact with substances with which they can couple, most typically polar molecules or ionic species, the microwaves can immediately create a large amount of kinetic energy in such species, which can provide sufficient energy to initiate or accelerate various chemical reactions. Microwaves also have an advantage over conduction heating in that the surroundings do not need to be heated because the microwaves can react instantaneously with the desired species.
The term “microwaves” refers to that portion of the electromagnetic spectrum between about 300 and 300,000 megahertz (MHz) with wavelengths of between about one millimeter (1 mm) and one meter (1 m). These are, of course, arbitrary boundaries, but help quantify microwaves as falling below the frequencies of infrared (IR) radiation and above those referred to as radio frequencies. Similarly, given the well-established inverse relationship between frequency and wavelength, microwaves have longer wavelengths than infrared radiation, but shorter than radio frequency wavelengths.
Because of their wavelength and energy, microwaves have been historically most useful in driving robust reactions or reactions in relatively large sample amounts, or both. Stated differently, the wavelengths of most microwaves tend to create multi-mode situations in cavities in which the microwaves are being applied. In a number of types of chemical reactions, this offers little or no disadvantage, and microwave techniques are commercially well established for reactions such as digestion or loss-on-drying moisture content analysis.
Relatively robust, multi-mode microwave techniques, however, tend to be less successful when applied to small samples of materials. Although some chemistry techniques have the obvious goal of scaling up a chemical reaction, in many laboratory and research techniques, it is often necessary or advantageous to carry out chemical reactions on small samples. For example, the availability of some compounds may be limited to small samples. In other cases, the cost of reactants may discourage large sample sizes. Other techniques, such as combinatorial chemistry, use large numbers of small samples to rapidly gather a significant amount of information, and then tailor the results to provide the desired answers, such as preferred candidates for pharmaceutical compounds or their useful precursors.
Microwave devices with larger, multimode cavities that are suitable for other types of microwave-assisted techniques (e.g., drying, digestion, etc.) are generally less-suitable for smaller organic samples because the power density pattern in the cavity is relatively non-uniform.
Accordingly, the need for more focused approaches to microwave-assisted chemistry has led to improvements in devices for this purpose. For example, in the commercially available devices sold under the assignee's (CEM Corporation, 3100 Smith Farm Road, Matthews, N.C. 28106) DISCOVER®, EXPLORER®, VOYAGER®, NAVIGATOR™, LIBERTY™, and INVESTIGATOR™ trademarks have provided single mode focused microwave devices that are suitable for small samples and for sophisticated reactions such as chemical synthesis.
The very success of such single mode devices has, however, created associated problems. In particular, the improvement in power density provided by single-mode devices can cause significant heating in small samples, including undesired over-heating in some circumstances. The ability to monitor the temperature of a microwave assisted chemical reaction aids in avoiding these difficulties.
One technique for monitoring a temperature change is through the use of infrared (IR) temperature monitoring. An IR detector monitors infrared radiation emitted by the vessel or its contents and can do so without directly contacting the vessel. Accordingly, the detector can be located in a position, either inside or near the cavity, that avoids interference with microwaves. Infrared temperature monitoring can also produce a measurement that is more representative of the entire sample, whereas traditional thermometers and temperature probes can tend to produce temperature measurements for primarily localized areas.
Moreover, because infrared radiation, as previously discussed, has different wavelengths than microwaves, the detector can accurately measure the temperature of the emitted infrared radiation without interfering with the microwave heating process, or vice versa. Temperature probes and traditional thermometers may be affected by microwave heating, resulting in the addition of extra heat to the sample or an inaccurate temperature reading.
As is known to those having ordinary skill in the art, organic reactions are often monitored visually to detect, for example, a color change or the presence of a precipitate. These physical changes are often indicative of the progress of a reaction, including completion, and can aid in determining the time of reaction (rate). For example, lack of a physical change could indicate that more time is needed. Conversely, a physical change occurring earlier than expected could indicate a faster reaction time. The ability to recognize a delayed or early reaction during heating enables the chemist to save time, either by stopping a reaction or by continuing the reaction, thereby avoiding the necessity of repeating the reaction with a longer reaction time. Other physical or chemical changes that are beneficially observed visually include changes in absorbance, emission, light scattering, and turbidity.
The capability to observe visible changes (or the lack thereof) in an ongoing reaction can also provide the opportunity to avoid undesired side reactions and to evaluate and identify optimum reaction conditions, particularly including optimum temperatures or temperature ranges.
Most single mode microwave instruments, however, require closed cavities, thus making direct visual observation of reactions difficult or impossible. Furthermore, a microwave cavity must internally reflect, rather than transmit, the relevant wavelengths of electromagnetic radiation. Thus, cavity walls transparent to visual radiation will generally be (unfavorably) transparent to microwave radiation as well. A transparent cavity will not, of course, contain microwave radiation, regardless of mode.
As an independent problem, and even if cavity walls or wall portions offer some visibility (as in the screened doors of many domestic kitchen microwave ovens), the light sources providing the illumination, such as incandescent, fluorescent, and other common visual sources, often include an infrared component. The presence of the infrared component can—and typically will—interfere with or saturate an infrared temperature detector, thereby compromising or defeating its performance.